Thermodynamics of the interaction between spike protein of severe acute respiratory syndrome-coronavirus-2 and the receptor of human angiotensin converting enzyme 2. Effects of possible ligands
Authors
García Iriepa, Cristina; Hognon, Cécilia; Frances-Monerris, Antonio; Iriepa Canalda, Isabel; Miclot, Tom; [et al.]Identifiers
Permanent link (URI): http://hdl.handle.net/10017/59525DOI: 10.1021/acs.jpclett.0c02203
ISSN: 1948-7185
Date
2020-11-05Affiliation
Universidad de Alcalá. Departamento de Química Analítica, Química Física e Ingeniería Química; Universidad de Alcalá. Departamento de Química Orgánica y Química InorgánicaBibliographic citation
The Journal of Physical Chemistry Letters, 2020, v. 11, n. 21, p. 9272-9281
Document type
info:eu-repo/semantics/article
Version
info:eu-repo/semantics/aceptedVersion
Rights
Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0)
© American Chemical Society, 2020
Access rights
info:eu-repo/semantics/openAccess
Abstract
Since the end of 2019, the coronavirus SARS-CoV-2 has caused more than 1000000 deaths all over the world and still lacks a medical treatment despite the attention of the whole scientific community. Human angiotensin-converting enzyme 2 (ACE2) was recently recognized as the transmembrane protein that serves as the point of entry of SARS-CoV-2 into cells, thus constituting the first biomolecular event leading to COVID-19 disease. Here, by means of a state-of-the-art computational approach, we propose a rational evaluation of the molecular mechanisms behind the formation of the protein complex. Moreover, the free energy of binding between ACE2 and the active receptor binding domain of the SARS-CoV-2 spike protein is evaluated quantitatively, providing for the first time the thermodynamics of virus?receptor recognition. Furthermore, the action of different ACE2 ligands is also examined in particular in their capacity to disrupt SARS-CoV-2 recognition, also providing via a free energy profile the quantification of the ligand-induced decreased affinity. These results improve our knowledge on molecular grounds of the SARS-CoV-2 infection and allow us to suggest rationales that could be useful for the subsequent wise molecular design for the treatment of COVID-19 cases.
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